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Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus.

Haddad-Tóvolli R, Paul FA, Zhang Y, Zhou X, Theil T, Puelles L, Blaess S, Alvarez-Bolado G - Front Neuroanat (2015)

Bottom Line: The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation.Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions.Our data confirm the model and are explained by it.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology and Neuroanatomy, University of Heidelberg Heidelberg, Germany.

ABSTRACT
Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR) of transcription factors Gli2 and Gli3. This balance-the Shh-Gli code-is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e., we wanted to approach the question of a possible hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1) hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; (2) another source of diversity are differential requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor domain known to depend on Gli2 for its development generates several essential hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

No MeSH data available.


Related in: MedlinePlus

Hypothalamic regions. (A) Conventional representation of the hypothalamus (gray) as ventral region with four rostro-caudal regions, POA, preoptic; ANT, anterior; TUB, tuberal; MAM, mamillary. (B) Model of the hypothalamus considering Shh expression (pink) as basal (ventral) marker. The POA is part of the telencephalon; the alar hypothalamus (yellow) corresponds to the anterior region; the tuberal and mamillary regions are not “caudal” but basal (ventral). ac, anterior commissure; hp, hypophysis; PTh, prethalamus; ZLI, zona limitans.
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Figure 1: Hypothalamic regions. (A) Conventional representation of the hypothalamus (gray) as ventral region with four rostro-caudal regions, POA, preoptic; ANT, anterior; TUB, tuberal; MAM, mamillary. (B) Model of the hypothalamus considering Shh expression (pink) as basal (ventral) marker. The POA is part of the telencephalon; the alar hypothalamus (yellow) corresponds to the anterior region; the tuberal and mamillary regions are not “caudal” but basal (ventral). ac, anterior commissure; hp, hypophysis; PTh, prethalamus; ZLI, zona limitans.

Mentions: The hypothalamus regulates homeostasis, endocrine secretion, and reproductive behavior (Saper, 2006; Puelles et al., 2012; Sternson, 2013) and its alterations can cause conditions like obesity and high blood pressure (Caqueret et al., 2005; McMillen et al., 2008). Complex gene expression pattern combinations underlie hypothalamic regional specification (Shimogori et al., 2010; Puelles et al., 2012). On the basis of classical neuroanatomy studies, the adult hypothalamus has been traditionally described as subdivided into four regions (preoptic, anterior, tuberal, and mamillary) arranged rostro-caudally and ventrally in the brain (Figure 1A) and flanked by the lateral hypothalamic area (LHA), a large region essential to regulate behavioral state and arousal (Swanson, 1987). The modern view considers the adult hypothalamus as part of a behavioral control column (Swanson, 2000).


Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus.

Haddad-Tóvolli R, Paul FA, Zhang Y, Zhou X, Theil T, Puelles L, Blaess S, Alvarez-Bolado G - Front Neuroanat (2015)

Hypothalamic regions. (A) Conventional representation of the hypothalamus (gray) as ventral region with four rostro-caudal regions, POA, preoptic; ANT, anterior; TUB, tuberal; MAM, mamillary. (B) Model of the hypothalamus considering Shh expression (pink) as basal (ventral) marker. The POA is part of the telencephalon; the alar hypothalamus (yellow) corresponds to the anterior region; the tuberal and mamillary regions are not “caudal” but basal (ventral). ac, anterior commissure; hp, hypophysis; PTh, prethalamus; ZLI, zona limitans.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373379&req=5

Figure 1: Hypothalamic regions. (A) Conventional representation of the hypothalamus (gray) as ventral region with four rostro-caudal regions, POA, preoptic; ANT, anterior; TUB, tuberal; MAM, mamillary. (B) Model of the hypothalamus considering Shh expression (pink) as basal (ventral) marker. The POA is part of the telencephalon; the alar hypothalamus (yellow) corresponds to the anterior region; the tuberal and mamillary regions are not “caudal” but basal (ventral). ac, anterior commissure; hp, hypophysis; PTh, prethalamus; ZLI, zona limitans.
Mentions: The hypothalamus regulates homeostasis, endocrine secretion, and reproductive behavior (Saper, 2006; Puelles et al., 2012; Sternson, 2013) and its alterations can cause conditions like obesity and high blood pressure (Caqueret et al., 2005; McMillen et al., 2008). Complex gene expression pattern combinations underlie hypothalamic regional specification (Shimogori et al., 2010; Puelles et al., 2012). On the basis of classical neuroanatomy studies, the adult hypothalamus has been traditionally described as subdivided into four regions (preoptic, anterior, tuberal, and mamillary) arranged rostro-caudally and ventrally in the brain (Figure 1A) and flanked by the lateral hypothalamic area (LHA), a large region essential to regulate behavioral state and arousal (Swanson, 1987). The modern view considers the adult hypothalamus as part of a behavioral control column (Swanson, 2000).

Bottom Line: The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation.Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions.Our data confirm the model and are explained by it.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Cell Biology and Neuroanatomy, University of Heidelberg Heidelberg, Germany.

ABSTRACT
Secreted protein Sonic hedgehog (Shh) ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR) of transcription factors Gli2 and Gli3. This balance-the Shh-Gli code-is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e., we wanted to approach the question of a possible hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: (1) hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; (2) another source of diversity are differential requirements for Shh of neural vs. non-neural origin; (3) the medial progenitor domain known to depend on Gli2 for its development generates several essential hypothalamic nuclei plus the pituitary and median eminence; (4) the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

No MeSH data available.


Related in: MedlinePlus